Acquired immune deficiency syndrome (AIDS) is recognized as one of the greatest health threats facing modern medicine. There is, as yet, no cure for this disease.
In 1983-1984, three groups independently identified the suspected etiological agent of AIDS. See, e.g., Barre-Sinoussi et al. (1983) Science 220:868-871; Montagnier et al., in Human T-Cell Leukemia Viruses (Gallo, Essex & Gross, eds., 1984); Vilmer et al. (1984) The Lancet 1:753; Popovic et al. (1984) Science 224:497-500; Levy et al. (1984) Science 225:840-842. These isolates were variously called lymphadenopathy-associated virus (LAV), human T-cell lymphotropic virus type III (HTLV-III), or AIDS-associated retrovirus (ARV). All of these isolates are strains of the same virus, and were later collectively named Human Immunodeficiency Virus (HIV). With the isolation of a related AIDS-causing virus, the strains originally called HIV are now termed HIV-1 and the related virus is called HIV-2. See, e.g., Guyader et al. (1987) Nature 326:662-669; Brun-Vezinet et al. (1986) Science 233:343-346; Clavel et al. (1986) Nature 324:691-695.
Since the implementation of highly active antiretroviral therapy (HAART) in the United States in 1996, the number of persons diagnosed with acquired immunodeficiency syndrome (AIDS) and the number of deaths among persons with AIDS have declined substantially (Karon et al. (2001) Am J Public Health 91(7):1060-1068) as a result, the number of persons living with AIDS has increased. The Centers for Disease Control (CDC) estimates that as of Dec. 31, 2000, approximately 340,000 persons in the United States were living with AIDS. (MMWR, Centers for Disease Control and Prevention. HIV/AIDS Surveillence Report, 13(No. 1) 2001).
Clinical trials in the US have been conducted with a limited number of subjects and further HIV vaccine development will require the identification of a suitable population where the HIV seroincidence is sufficiently high to enable a distinction between protection in the immunized population with a placebo control. Seage III et al. (2001) Am. J. Epidemiol. 153(7):619-627; Halpern et al. (2001) J Acquir Immune Defic Syndr 27(3):281-8.
The primary mode of transmission of HIV is through sex and by contact with infected body fluids including blood, semen, vaginal fluid, breast milk, and other body fluids containing blood. In industrialized countries, the majority of cases reported in which the person's risk is known are among men who have sex with men. Before blood screening for antibodies to HIV was instituted, transfusion-associated HIV was a concern in the US. (CDC. Update: HIV-2 infection among blood and plasma donors—United States, June 1992-June 1995. MMWR, 1995. 44: p. 603-606). Other modes of transmission include needle sharing by injection drug users, inadvertent contact with infected blood among hospital workers, and rare iatrogenic transmission through the re-use of contaminated medical equipment. Higher rates of sexually transmitted infections signal a rise in unsafe sex practices. Chen et al. (2001) Am J Public Health 92(9):1387-1388. Heterosexual transmission of HIV-1 continues to rise, particularly among women, the young, and the economically disadvantaged and, in fact, heterosexual transmission is the dominant mode of transmission in the developing world. These trends highlight the need for the development of a preventive and/or therapeutic vaccine. Catania et al. (2001) Am J Public Health 91(6):907-914.
Several targets for vaccine development have been examined, including the env and Gag gene products encoded by HIV. Gag gene products include, but are not limited to, Gag-polymerase (pol) and Gag-protease (prot). Env gene products include, but are not limited to, monomeric gp120 polypeptides, oligomeric gp140 polypeptides (o-gp140) and gp160 polypeptides.
Recently, use of HIV Env polypeptides in immunogenic compositions has been described. (see, U.S. Pat. No. 5,846,546 to Hurwitz et al., issued Dec. 8, 1998, describing immunogenic compositions comprising a mixture of at least four different recombinant virus that each express a different HIV env variant; and U.S. Pat. No. 5,840,313 to Vahlne et al., issued Nov. 24, 1998, describing peptides which correspond to epitopes of the HIV-1 gp120 protein). In addition, U.S. Pat. No. 5,876,731 to Sia et al, issued Mar. 2, 1999 describes candidate vaccines against HIV comprising an amino acid sequence of a T-cell epitope of Gag linked directly to an amino acid sequence of a B-cell epitope of the V3 loop protein of an HIV-1 isolate containing the sequence GPGR. However, these groups did not identify an effective HIV vaccine.
U.S. Pat. No. 6,602,705 and International Patent Publications WO 00/39302; WO 02/04493; WO 00/39303; and WO 00/39304 describe polynucleotides encoding immunogenic HIV polypeptides from various subtypes.
Thus, there remains a need for immunogenic HIV compositions, specifically for HIV vaccine formulations.